Short summary

Anorexia nervosa (AN) has the highest mortality of all mental illnesses. Sudden death due to thromboembolic events in patients with AN has been reported. The incidence of thromboembolic (TE) events and the hemostatic balance in patients with anorexia nervosa are sparsely investigated. This study will determine the incidence of TE events in patients with AN compared to the background population and thoroughly to characterize the hemostatic balance in AN compared to normal-weight women.

Rationale

BACKGROUND

Anorexia nervosa (AN) is a complex psychiatric disorder with concomitant medical complications to malnutrition and starvation and it is associated with the highest mortality of the mental illnesses.

It is estimated that one-third of all deaths in patients with AN are due to cardiac causes, mainly sudden death, and alterations in cardiac electrical activity, structure and hemodynamics have been suggested as mortality causes. Thrombotic disorders such as myocardial infarction, stroke, and pulmonary embolism may also result in sudden cardiac death, and we have previously reported venous thromboembolism in four patients with AN

Whether a disturbed hemostatic balance is associated with re-nutrition, insulin sensitivity and cortisol in AN is unknown. The guidelines of thromboprophylaxis treatment may not be appropriate in this patient group due to metabolic and hemostatic disturbances and increased thrombotic risk of reasons related to refeeding syndrome not listed in current guidelines. To optimize guidelines for AN patients, new evidence is highly warranted

AIMS

This study aims to determine the incidence of venous and arterial thromboembolic events in patients with AN compared to the background population, to characterize the hemostatic balance in AN compared to normal-weight women, and to assess the associations between the hemostatic balance and nutritional status, insulin sensitivity and cortisol level in women with AN. The study will provide new knowledge which qualifies the work of preparing guidelines for thrombosis prophylactic intervention in this patient group.

RESEARCH QUESTIONS

1. Is the incidence of venous and arterial thromboembolism increased in patients diagnosed with AN compared to an age-matched control group?

2. Is the hemostatic balance disturbed in women with AN compared with healthy, normal-weight women?

3. Are cortisol, insulin sensitivity and nutritional status associated with alterations in biomarkers of the hemostatic balance in AN?

The research questions will be answered in three sub studies.

SUB STUDY 1

Sub study 1 will answer research question 1, determining if the incidence of venous and arterial thromboembolism is increased in patients with AN compared to an age-matched control group. The study is based on the comprehensive Danish registries. An already existing cohort of more than 7500 patients with AN will be evaluated for incidence of thromboembolic events and compared to an age-matched control group.

SUB STUDY 2

Sub study 2 will answer research question 2, exploring the hemostatic balance in patients with AN compared to healthy, normal-weight controls.

Patients with anorexia nervosa (n=40) will be recruited from the highly specialized Center of Eating Disorders at Odense University Hospital. Patients and controls will have blood samples drawn to evaluate the hemostatic balance using a large battery of hemostatic markers.

SUB STUDY 3

Sub study 3 will answer research question 3, clarifying associations between the hemostatic balance and cortisol, insulin sensitivity and nutritional status in AN. Participants of sub study 3 are the patients with AN from sub study 2. From further analysis of the blood samples and by answering validated questionnaires to determine nutritional status and AN severity, research question 3 will be answered.

Description of the cohort

Patients with anorexia nervosa (n=40) will be recruited from the highly specialized Center of Eating Disorders at Odense University Hospital. Controls will be recruited using social media.

Inclusion criteria, cases

• Fulfilling DSM-5 criteria for AN

• Age 18 - 40 years

• Female sex

Exclusion criteria, cases

• Somatic comorbidity requiring systemic medications

• Previous thromboembolic event and/or known genetic predisposition

• Use of p.o. hormonal contraception

• Smoking

Data and biological material

Data from registries

• Data on thromboembolic disorders

• Data on use of any prescription deemed

Biological material

• Blood samples

Somatic data

• Weight

• Height

Questionnaires

• Eating Disorder Inventory - third version (EDI-3)

Collaborating researchers and departments

The Nutritional Unit, Department of Endocrinology, Center for Eating Disorders, Odense University Hospital and Psychiatry in the region of Southern Denmark

• Jeanie Meincke Egedal, MD, PhD-student
• Professor René Klinkby Støving, MD, PhD

Unit for Thrombosis Research, Department of Clinical Biochemistry, Hospital of South West Jutland

• Associate professor Else Marie Bladbjerg, MSc, PhD

Department of Clinical Sciences, Umeå University

• Associate professor Jan Magnus Sjögren, MD, PhD

Department of Child and Adolescent Mental Health Odense, Mental Health Services in the Region of Southern Denmark

• Pia Veldt Larsen

Clinical Pharmacology and Pharmacy, University of Southern Denmark

• Professor Jesper Hallas, MD, PhD

The Nutritional Unit, Department of Endocrinology, Centre for Eating Disorders, Odense University Hospital